Cloning and characterization of Entamoeba histolytica antigens recognized by human secretory IgA antibodies

Carrero, Julio César; Petrossian, Pavel; Acosta, E.; Sánchez-Zerpa, Marı́a; Ortiz‐Ortiz, Librado; Laclette, Juan Pedro

doi:10.1007/s004360050052

Cited by 16 publications

(9 citation statements)

References 26 publications

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“…The catalytic activity of enolase in E. histolytica has been characterized [22], and it was found to be co-secreted with serpin and aldehyde alcohol dehydrogenase by activated trophozoites [23]. Indeed, antibodies against enolase have been detected in patients with amebiasis, and this suggests that enolase plays a role in the virulence of the parasite [33]. Such a role has been already reported in bacteria where enolase binds plasminogen [34].…”

Section: Discussionmentioning

confidence: 82%

A New Nuclear Function of the Entamoeba histolytica Glycolytic Enzyme Enolase: The Metabolic Regulation of Cytosine-5 Methyltransferase 2 (Dnmt2) Activity

Tovy¹,

Tov²,

Gaentzsch

et al. 2010

PLoS Pathog

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Cytosine-5 methyltransferases of the Dnmt2 family function as DNA and tRNA methyltransferases. Insight into the role and biological significance of Dnmt2 is greatly hampered by a lack of knowledge about its protein interactions. In this report, we address the subject of protein interaction by identifying enolase through a yeast two-hybrid screen as a Dnmt2-binding protein. Enolase, which is known to catalyze the conversion of 2-phosphoglycerate (2-PG) to phosphoenolpyruvate (PEP), was shown to have both a cytoplasmatic and a nuclear localization in the parasite Entamoeba histolytica. We discovered that enolase acts as a Dnmt2 inhibitor. This unexpected inhibitory activity was antagonized by 2-PG, which suggests that glucose metabolism controls the non-glycolytic function of enolase. Interestingly, glucose starvation drives enolase to accumulate within the nucleus, which in turn leads to the formation of additional enolase-E.histolytica DNMT2 homolog (Ehmeth) complex, and to a significant reduction of the tRNAAsp methylation in the parasite. The crucial role of enolase as a Dnmt2 inhibitor was also demonstrated in E.histolytica expressing a nuclear localization signal (NLS)-fused-enolase. These results establish enolase as the first Dnmt2 interacting protein, and highlight an unexpected role of a glycolytic enzyme in the modulation of Dnmt2 activity.

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Section: Discussionmentioning

confidence: 82%

A New Nuclear Function of the Entamoeba histolytica Glycolytic Enzyme Enolase: The Metabolic Regulation of Cytosine-5 Methyltransferase 2 (Dnmt2) Activity

Tovy¹,

Tov²,

Gaentzsch

et al. 2010

PLoS Pathog

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“…45 Furthermore, a known serine-rich protein isoform, a 29 kDa cysteine-rich protein, the α-and β-elongation factor, and the glutamic acid-peptide are recognized by sIgA antibodies. 46 IgA also inhibits amoebic proteolytic activities in vitro. 47 In asymptomatic carriers, the recognition of the E. histolytica 115-kDa surface protein by human sIgA has been reported.…”

Section: Amoebicidal Effect Of Human Milk Is Due To the Protein Fractmentioning

confidence: 96%

Amoebicidal Activity of Milk, Apo-lactoferrin, sIgA and Lysozyme

León-Sicairos¹,

López-Soto²,

Reyes-López³

et al. 2006

Clinical Medicine & Research

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Entamoeba histolytica is a pathogenic, parasitic protozoan that can infect the large intestine and cause amoebiasis, an illness responsible for at least 100,000 deaths annually worldwide. The capacity of human milk to kill amoebas 6,15 and the amoebicidal action of secretory immunoglobulin type A (sIgA) 16 have been reported. However, it is unknown which other components of milk are amoebicides. As milk contains several microbicidal components, we fractionated milk and tested each fraction against trophozoites in axenic cultures to describe any amoebicidal effects of other components of human and bovine milk such as lactoferrin, lysozyme and sIgA. We also sought to identify any combined effect among these molecules. Objectives: To identify amoebicidal components in human milk and the effect of iron on the amoebicidal activity. Original ResearchDesign: Investigation in axenic cultures of Entamoeba histolytica trophozoites.Methods: Amoebas were treated with 5%-20% of human, bovine and swine milk, with 10% of human milk fractions (i.e., casein, proteins except casein and fat) or with 1 mg/ml of human milk apo-lactoferrin, human secretory immunoglobulin type A (sIgA) and chicken egg-white lysozyme (i.e., purified proteins). Milk proteins were detected using immunoblot. Confocal microscopy was used to define the interaction of milk proteins (100 µM each) and amoebas. Experiments were done at least three times in triplicate, and mean and standard deviations were calculated.Results: Human and bovine milk were amoebicidal showing a concentration-dependent effect. The amoebicidal effect was increased in the absence of iron. Milk protein fractions, with the exception of casein, were the components responsible for the amoebicidal activity found. Apo-lactoferrin, sIgA and lysozyme were identified in the amoebicidal milk protein fraction. Apo-lactoferrin showed the major amoebicidal effect. These proteins, either alone or in combination, showed a killing effect on the trophozoites.They bound to the amoebic membrane causing cell rounding, lipid disruption and damage. Conclusions:Milk proteins such as apo-lactoferrin, sIgA and lysozyme are able to kill Entamoeba histolytica trophozoites.This study confirms the importance of feeding breast milk to newborns.

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“…Both proteins are highly immunogenic, conferring 50% and 100% of protection against ALA in gerbils, respectively (reviewed in (49,51)). Interestingly, both proteins were identified by immunoscreening with sIgA antibodies from saliva of patients with intestinal amoebiasis, suggesting that they are able to induce secretory immune responses in human mucosa (53). In addition, cytosolic proteins such as cyclophilin, 70 kDa heat‐shock protein, enolase, 1‐α elongation and ribosomal protein L23a were also recognized by the human sIgA antibodies, suggesting that internal amoebic antigens are also immunogenic at mucosal surfaces (53).…”

Section: Secretory Iga (Siga)‐based Vaccinementioning

confidence: 99%

“…Interestingly, both proteins were identified by immunoscreening with sIgA antibodies from saliva of patients with intestinal amoebiasis, suggesting that they are able to induce secretory immune responses in human mucosa (53). In addition, cytosolic proteins such as cyclophilin, 70 kDa heat‐shock protein, enolase, 1‐α elongation and ribosomal protein L23a were also recognized by the human sIgA antibodies, suggesting that internal amoebic antigens are also immunogenic at mucosal surfaces (53). With the exception of the Gal‐lectin, the potential of all this antigens in protection against intestinal amoebiasis has not been addressed.…”

Section: Secretory Iga (Siga)‐based Vaccinementioning

confidence: 99%

The role of the secretory immune response in the infection by Entamoeba histolytica

Carrero

Cervantes-Rebolledo

Aguilar-Díaz

et al. 2007

Parasite Immunology

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Intestinal infection with the protozoan parasite Entamoeba histolytica elicits a local immune response with rising of specific secretory IgA (sIgA) antibodies detectable in several compartments associated to mucosa. Anti-amoebic sIgA antibodies have been reported in faeces, saliva, bile and breast milk from dysenteric patients and research trying to elucidate their role in protection has recently intensified. IgA antibodies inhibit the in vitro adherence of E. histolytica trophozoites to epithelial cell monolayers by recognizing several membrane antigens, including the galactose-binding lectin (Gal-lectin), main surface molecule involved in adherence, and the serine and cystein-rich proteins, all of them potential vaccine candidates. In fact, the presence of sIgA anti-Gal lectin in faeces of patients recovered from amoebic liver abscess (ALA) was associated with immunity to E. dispar. Moreover, the combined nasal and intraperitoneal vaccination of C3H/HeJ mice with native and recombinant Gal-lectin protected mice against an intracecal challenge with virulent E. histolytica trophozoites, protection that seemed to be associated with the induction of specific intestinal sIgA antibodies. Therefore, the stimulation of intestinal secretory response by mucosal delivery of amoebic antigens has been positioned as a promising strategy for inducing protection against human amoebiasis.

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Cloning and characterization of Entamoeba histolytica antigens recognized by human secretory IgA antibodies

Cited by 16 publications

References 26 publications

A New Nuclear Function of the Entamoeba histolytica Glycolytic Enzyme Enolase: The Metabolic Regulation of Cytosine-5 Methyltransferase 2 (Dnmt2) Activity

A New Nuclear Function of the Entamoeba histolytica Glycolytic Enzyme Enolase: The Metabolic Regulation of Cytosine-5 Methyltransferase 2 (Dnmt2) Activity

Amoebicidal Activity of Milk, Apo-lactoferrin, sIgA and Lysozyme

The role of the secretory immune response in the infection by Entamoeba histolytica

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